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Tommy Hilfiger Profile
|Full Name:
|Tommy Hilfiger - Contact Tommy Hilfiger
Tommy Hilfiger News
CNBCTommy Hilfiger reinvented itself to create 'see-now-buy-now' shopping
The PVH-owned fashion label knew its consumers were getting older with the brand, and it needed to reinvent itself, so it created the real-time 'Tommy Now'
Tommy Hilfiger On Why Embracing Risk Is The Key To Innovation
United States Of America : The Chainsmokers are brand ...
Fibre2fashion.com all 4 news articles »
BillboardThe Chainsmokers Are Tommy Hilfiger Brand Ambassadors | Billboard
Beyond dominating the 2017 Billboard Music Awards with 22 nominations (and three wins) and electrifying sets for their Memories Do Not Open tour -- which ...
The Chainsmokers Have a New Fashion Gig
Hollywood Reporter
The Chainsmokers Named Tommy Hilfiger's Newest Global ... - People
The Chainsmokers Named Tommy Hilfiger's Global Menswear ...
TeenVogue.com HarpersBazaarArabia- EDM Sauce- News18 all 16 news articles »
Los Angeles TimesTommy Hilfiger to take fall show with Gigi Hadid to London
Los Angeles Times
Tommy Hilfiger will touch down in London for his next ?see-now-buy-now? runway event. Following fashion shows the last two seasons in New York and Los Angeles, Hilfiger will stage his TommyNow experiential runway event on Tuesday, Sept. 19, at 7 p.m. ...
News Bites | Tommy Hilfiger Heads to London, Coveteur Names A-List Advisors
The Business of Fashion
Tommy Hilfiger and Gigi Hadid Head to London for Their Next Runway Show
Hollywood Reporter
Gigi Hadid and Tommy Hilfiger's Next Traveling Runway Spectacular Will Be in London
W Magazine InStyle- ELLE.com- Footwear News all 20 news articles »
- BoF Exclusive | Tommy Hilfiger Names The Chainsmokers Global Menswear Ambassadors - The Business of Fashion
The Business of FashionBoF Exclusive | Tommy Hilfiger Names The Chainsmokers Global Menswear Ambassadors
The Business of Fashion
NEW YORK, United States ? One month after extending its partnership with ambassador and ?Tommy Girl? Gigi Hadid for an additional two years, Tommy Hilfiger is signing on a pair of influential chart-toppers to boost its menswear business. Starting in ...
Tommy Hilfiger Announces the Chainsmokers as Global Brand ...
Business Wire (press release) all 5 news articles »
- Tommy Hilfiger: The Great Retail Shakeout Will Continue, With the Strong Getting Even Stronger - TheStreet.com
TheStreet.comTommy Hilfiger: The Great Retail Shakeout Will Continue, With the Strong Getting Even Stronger
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Independent OnlineThe Chainsmokers are the new face of Tommy Hilfiger
Independent Online
Speaking about Tommy Hilfiger's new representatives, the creative mastermind said: "Alex and Drew are truly the perfect definition of today's Tommy Guy ? their talent, optimism, unique sound and effortless cool have made them standout in the music world.".
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National Post
NEW YORK ? Many designers like to add some theatrical flair to their runway shows. But taking over a whole New York City pier to stage a carnival?
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Your EDMThe Chainsmokers Are The New Faces of Iconic Fashion Brand ...
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The Chainsmokers are heading up a campaign for a throwback, yet classic clothing brand -- Tommy Hilfiger. Fusion of fashion and music has been heavily inco.
Tommy Hilfiger picks Chainsmokers as ambassadors - Trade Arabia
Trade Arabia
The Chainsmokers land a major deal with Tommy Hilfiger - CelebMix
CelebMix (blog) all 3 news articles »
BuzzFeed NewsOMG, Ivanka Trump Was Once A Model For Tommy Hilfiger In The '90s
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As you might already know, designer Tommy Hilfiger is no stranger to having celebrity offsprings appear as models in his runway shows and ad campaigns.
Tommy Hilfiger Will Show #TommyNow in London | HYPEBAE
HYPEBAE all 3 news articles »


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Composite Wood Decking Materials OptionsPosted on 11:51 pm | Posted in WPC Decking Blog | Posted by
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A number of studies have examined the relationship between the expression of the class III β-tubulin (TUBB3) and the treatment responses to the taxane/vinorebine-based chemotherapy in patients with non-small cell lung cancer (NSCLC). However, the results of these studies were inconsistent and inconclusive. Therefore, we conducted an up-to-date meta-analysis to evaluate the prognostic role of TUBB3 in the taxane/vinorebine-based chemotherapy.
A literature search for relevant studies was conducted in PubMed, Embase, and CNKI. The inclusion criteria were the taxane/vinorebine-based chemotherapy in patients with NSCLC and the evaluation of the clinical outcomes in relation to the expression of TUBB3. The clinical outcomes analyzed in this study included the overall response rate (ORR), overall survival (OS), and event-free survival (EFS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the risk associated with the TUBB3 expression in the taxane/vinorebine-based chemotherapy.
A total of 28 studies with 2401 NSCLC patients were qualified for this meta-analysis. We found that the positive or high level of TUBB3 expression was associated with a poorer ORR (OR = 0.24, 95% CI = 0.16–0.36, p<0.001), an unfavorable OS (HR = 1.52, 95% CI = 1.27–1.82, p<0.001), and a worse EFS (HR = 1.47, 95% CI = 1.24–1.74, p<0.001) compared to the negative or low level of TUBB3 expression. The statistically significant associations between TUBB3 and chemotherapy responses were also observed in the stratified subgroup analysis, which included the analysis by ethnic subgroup (Asian and Caucasian), chemotherapy regimen (taxane-based and vinorebine-based), TUBB3 detection method (IHC and PCR), and treatment strategy (surgery plus adjuvant chemotherapy and palliative chemotherapy).
Citation: Yang Y-L, Luo X-P, Xian L (2014) The Prognostic Role of the Class III β-Tubulin in Non-Small Cell Lung Cancer (NSCLC) Patients Receiving the Taxane/Vinorebine-Based Chemotherapy: A Meta-Analysis. PLoS ONE 9(4): e93997. https://doi.org/10.1371/journal.pone.0093997
Editor: Natasha Kyprianou, University of Kentucky College of Medicine, United States of America
Received: September 28, 2013; Accepted: March 10, 2014; Published: April 4, 2014
Copyright: © 2014 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Guangxi Scientific Research and Technology Development projects (grant no. 10124001A-592 44). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Lung cancer is the most common type of cancer and a leading cause of cancer-related death for both men and women worldwide [1]. The non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Two-thirds of NSCLC cases are diagnosed at advanced stages because the patients are typically asymptomatic at early stages [2]. Due to the recent advancements in the surgical techniques and chemoradiation therapy, the one-year relative survival rate for lung cancer has increased from 35.7% to 44.5% [3]. However, the prognosis of lung cancer, especially for the advanced stage of NSCLC, is still poor. The high morbidity and mortality rates of lung cancer has continued to be a major public health concern worldwide [4].
Approximately half of NSCLC patients receive chemotherapy as part of their treatments, indicating that chemotherapy has become a common treatment method for NSCLC [5]. However, chemoresistance has emerged to be a major problem that has greatly limited the benefits of chemotherapy in patients with NSCLC [5], [6]. The clinical outcomes of chemotherapy are usually very heterogeneous and unpredictable even in NSCLC patients with similar clinical and pathologic features [7]. In addition, chemoresistance results in a waste of public health budget and makes patients suffer from unnecessary adverse effects of chemotherapy [8]. Since genetic factors may play an important role in the development of chemoresistance, it would be of great value to identify useful biomarkers that can predict the clinical outcomes of chemotherapy in NSCLC [8].
Tubulin-binding agents (TBAs), such as taxanes (paclitaxel, docetaxel) and vinca alkaloids (vinorelbine, vincristine), have been widely used in the treatment of NSCLC [9]–[11]. These agents block cell division by inhibiting the mitotic spindles. Previous in vitro studies have shown that high level of class III β-tubulin (TUBB3) expression was associated with chemoresistance to paclitaxel, docetaxel, and vinblastine [12]. On the basis of these preclinical results, several studies have investigated the clinical role of TUBB3 in various human cancers, mostly in NSCLC [12]–[15]. To date, a large number of clinical studies have examined the relationship between the expression of TUBB3 and the clinical outcomes of taxane/vinorebine-based chemotherapy in patients with NSCLC. However, the results were still inconclusive [16]–[43]. Some studies showed a significant association between TUBB3 and taxane/vinorebine-based chemotherapy, while the others found no correlation. Considering the relatively small sample size and the limited statistical power of an individual study, it is necessary to conduct a comprehensive up-to-date meta-analysis to evaluate the association between the expression of TUBB3 and the clinical outcomes of chemotherapy, such as the objective response rate (ORR), overall survival (OS), and event-free survival (EFS) in NSCLC patients receiving the taxane/vinorebine-based chemotherapy.
Materials and Methods
Literature search strategy
Relevant studies published before August 2013 were retrieved from online databases, including the PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) using the following terms and combinations: "class III β-tubulin" or "tubulin" or "TUBB3" or "lung cancer" or "neoplasm, lung". The search was limited to full-text papers written in English or Chinese. Furthermore, the references of the retrieved studies were manually screened for additional relevant studies. If necessary, the authors of the original articles were contacted for additional data, such as the relationship between the expression level of TUBB3 and the ORR, OS, and EFS.
Inclusion and exclusion criteria
Eligible studies were identified according to the following criteria: (1) human-based investigations; (2) pathologically confirmed non-small cell lung cancer; (3) articles published in English or Chinese; (4) taxane/vinorebine-based chemotherapy treatment; (5) investigation of the association between the expression of class III β-tubulin and the clinical outcomes of chemotherapy, including the ORR, OS, and EFS (including progression-free survival (PFS), disease-free survival (DFS), and recurrence-free survival (RFS)); (6) the full-text of the published articles were available. The exclusion criteria were as the follows: (1) patients younger than 18 years old; (2) studies in which necessary data were not provided; (3) for overlapped studies, the studies with a smaller dataset were excluded.
Data extraction
Two investigators (YL Yang and XP Luo) independently extracted the following information from the qualified publications: surname of the first author, publication year, country, ethnicity, sample size, disease stage, ECOG performance status, chemotherapy regimen, detection method of TUBB3, and clinical outcome (ORR, OS, or EFS). All data were then examined by two investigators independently (YL Yang and XP Luo). Disagreements between the investigators were resolved by discussion. When necessary, a third investigator (L Xian) helped to reach a consensus with all investigators.
Quality Assessment
The quality of the methodology of the included studies was assessed by the Newcastle-Ottawa scale (NOS) recommended by the Cochrane Non-Randomized Studies Methods Working Group [44]. Studies with five or more stars were defined as high quality studies. Quality assessment was performed by two investigators (YL Yang and XP Luo) independently. Disagreements were resolved by discussion.
Statistical analysis
The ORR was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria [45] or the World Health Organization (WHO) criteria (Good response = complete response + partial response; poor response = stable disease + progressive disease) [46]. The HRs and their 95% CIs for the OS and EFS were directly extracted from reports, or indirectly estimated from the Kaplan-Meier curves, or calculated by methods described by Tierney [47]. The association between the expression of TUBB3 and the clinical responses to the taxane/vinorebine-based chemotherapy was evaluated by the odds ratio (OR) with 95% CIs in the following comparison: high or positive expression of TUBB3 vs. low or negative expression of TUBB3. For the OS and EFS, the pooled HRs and 95% CIs were calculated from the HRs and 95% CIs extracted from each eligible study. Heterogeneity between studies was detected by the Q test and the I2 metric (no heterogeneity: I2 = 0%–25%; moderate heterogeneity: 25%–50%; large heterogeneity: 50%–75%; and extreme heterogeneity: 75%–100%) [48]. A fixed effect model analysis was performed when p≥0.10 in the Q test or when I2<50% [49], otherwise a random effect model analysis was conducted [50]. Subgroup analyses by ethnicity (Asian or Caucasian), chemotherapy regimen (taxane alone, vinorebine alone, or taxane and vinorebine combined), TUBB3 detection method (IHC, PCR, or Western blot), and treatment strategy (surgery plus adjuvant chemotherapy or palliative chemotherapy) were also performed. Publication bias were tested by the Begg's funnel plot [51] and the Egger's test [52]. All p values were two-tailed and a p value less than 0.05 was considered statistically significant. Most of the statistical analyses in this study were conducted by the STATA software (version 11.2; StataCorp, College Station, Texas USA).
Eligible Studies
A total of 522 studies were identified in the initial search from the three databases (PubMed, EMBASE, and CNKI). The detailed procedure of literature search was shown in Figure.1. After examining the titles and abstracts, 477 articles were excluded because they were irrelevant to this meta-analysis. The full texts of the rest 45 potentially relevant studies were carefully reviewed. As a result, 17 out of the 45 studies were excluded because of the following reasons: not taxane/vinorebine-based treatment (n = 3), data overlapping (n = 5), insufficient information (n = 4), in vitro chemosensitivity assay (n = 3), and TUBB3-tailored chemotherapy (n = 2). Therefore, 28 studies including 2401 patients were qualified for this meta-analysis [16]–[43]. The baseline characteristics of all eligible studies were reported in Table 1. The patient sample size of the included studies ranged from 19 to 577. There were 9 studies conducted in the Caucasian population [16]–[20], [27]–[30]; 19 studies were conducted in the Asian population [21]–[26], [31]–[43]; and two studies were conducted in multiple ethnicities. Several methods were used to assess the expression of TUBB3: immunohistochemistry (IHC) in 25 studies [16]–[30], [32]–[34], [36]–[42], polymerase chain reaction (PCR) in two studies [16], [32], and Western blot in one study [36] (Table 1). All relevant studies were assessed by the NOS quality scale and all eligible studies scored highly (with five stars or more). The quality score of the eligible studies can be found in Table S1.
Objective response rate
The association between the expression of TUBB3 and the treatment response to the taxane/vinorebine-based chemotherapy was investigated in 18 studies which consisted of 954 patients [16]–[19], [22], [23], [27], [31], [34]–[43]. We found that the positive or high level of TUBB3 expression was significantly associated with a worse response to chemotherapy when compared to the negative or low level of TUBB3 in the random model analysis (positive/high vs. negative/low: OR = 0.24, 95% CI = 0.16–0.36, p<0.001; I2 = 38.6%, P = 0.05 for heterogeneity, Table 2, Figure. 2).
Stratified subgroup analysis by ethnicity, chemotherapy regimen, and TUBB3 detection method were also performed in this meta-analysis. There were 13 investigations for the Asian population that were comprised of 758 cases [22], [23], [31], [34]–[43]. In addition,five studies composed of 196 cases were conducted in the Caucasian population [16]–[19], [27]. Ethnic subgroup analysis indicated that the negative or low level of TUBB3 expression was correlated with a better chemotherapy response in both Asian (OR = 0.23, 95% CI = 0.15–0.36, p<0.001; I2 = 37.2%, P = 0.09 for heterogeneity) and Caucasian patients (OR = 0.26, 95% CI = 0.09–0.79, p = 0.02; I2 = 51.3%, P = 0.08 for heterogeneity, Table 2).
In the subgroup analysis by the chemotherapy regimens, 13 studies used the taxane-based regimens [16], [18], [19], [22], [23], [35], [37]–[43], four studies investigated the vinorebine-based regimens [16], [17], [36], [43], and one study examined both taxane and vinorebine-based regimens [34]. The studies by Rosell [16] and Liu [43] reported both the patients receiving the taxane-based regimen and the vinorebine-based regimen. The study by Xiao [34], however, did not provide sufficient information to distinguish the patients receiving the taxane-based chemotherapy from the patients receiving the vinorebine-based chemotherapy. Our analysis suggested that the negative or low level of TUBB3 expression showed a better response than the positive or high level of TUBB3 expression in the taxane-based regimen (positive/high vs. negative/low: OR = 0.18, 95% CI = 0.12–0.25, p<0.001; I2 = 23,4%, P = 0.21 for heterogeneity) and the vinorebine-based regimen (positive/high vs. negative/low: OR = 0.54, 95% CI = 0.31–0.93, p = 0.03; I2 = 0.0%, P = 0.72 for heterogeneity). However, these associations were not found in Xiao's study, in which the analysis results were based on a mixed patient population receiving either the taxane- or vinorebine-based regimens (positive/high vs. negative/low: OR = 0.34, 95% CI = 0.11–1.07, p = 0.065, Table 2) [34].
In this study, 14 studies used IHC [17]-[19], [22], [23], [34], [35], [37]-[41], [43], one study used PCR [16], and one study used Western Blot [36] to detect the expression of TUBB3. Only the studies using IHC showed a significant association between the expression of TUBB3 and the ORR in patients with NSCLC (OR = 0.22, 95% CI = 0.14–0.34, p<0.001; I2 = 39.4%, P = 0.06 for heterogeneity, Table 2).
Except for the study by Azuma K et al. that reported patients receiving surgery plus adjuvant chemotherapy [22], the rest of the studies reported patients receiving palliative chemotherapy [16]–[19], [23], [27], [31], [34]–[43]. Our analysis suggested that the patients with negative or low level of TUBB3 expression had a better treatment response than those with positive or high level of TUBB3 expression in the palliative taxane/vinorebine-based chemotherapy (OR = 0.23, 95% CI = 0.14–0.37, p<0.001; I2 = 46.7%, P = 0.04 for heterogeneity, Table 2).
Overall survival
18 studies including 1879 patients evaluated the association between the expression of TUBB3 and the OS in NSCLC patients receiving the taxane/vinorebine-based chemotherapy [17], [19]–[35]. The pooled analysis indicated that the patients with positive or high level of TUBB3 had a shorter OS than the patients with negative or low level of TUBB3 (positive/high vs. negative/low: HR = 1.52, 95% CI = 1.27–1.82, p<0.001; I2 = 38.0%, P = 0.05 for heterogeneity, Table 2, Figure 3).
In the stratified analysis by ethnicity, we found that the expression of TUBB3 was correlated with the OS in both Asian [21]–[26], [31]–[35] (HR = 1.48, 95% CI = 1.21–1.82, p<0.001; I2 = 13.2%, P = 0.31 for heterogeneity) and Caucasian patients [17], [19], [20], [27]–[30] (HR = 1.48, 95% CI = 1.14–1.92, p = 0.004; I2 = 55.6%, P = 0.04 for heterogeneity, Table 2). In the subgroup analysis by chemotherapy regimen, ten studies investigated the taxane-based regimens [19], [21]–[23], [25], [26], [30], [31], [35], [53]; four reported the vinorebine-based regimens [17], [20], [32], [33]; and four studies examined both regimens [27]–[29], [34]. The results of our analysis showed that the negative or low TUBB3 expression was associated with a longer OS than the positive or high TUBB3 expression in NSCLC patients receiving the taxane-based, or vinorebine-based, or both taxane- and vinorebine-based regimens (taxane regimen: HR = 2.06, 95% CI = 1.57–2.72, p<0.001; I2 = 0.0%, P = 0.71 for heterogeneity; vinorebine regimen: HR = 1.45, 95% CI = 1.17–1.79, p = 0.001; I2 = 37.6%, P = 0.19 for heterogeneity; taxane and vinorebine combined regimen: HR = 1.19, 95% CI = 1.01–1.41, p = 0.038; I2 = 39.4%, P = 0.18 for heterogeneity, Table 2). The subgroup analysis of the TUBB3 detection methods indicated that the expression of TUBB3 was significantly associated with the OS in the 16 studies using IHC as the detection method for TUBB3 [17], [19]–[23], [25]–[30], [33], [35], [53] (HR = 1.55, 95% CI = 1.25–1.93, p<0.001; I2 = 44.0%, P = 0.03 for heterogeneity), as well as in the two studies using PCR [30], [32] (HR = 1.54, 95% CI = 1.18–1.99, p = 0.001; I2 = 0.0%, P = 0.85 for heterogeneity, Table 2). Additional stratified analysis based on the treatment strategy showed that the expression of TUBB3 could be used as a prognostic biomarker to predict the clinical outcomes in patients treated by surgery plus adjuvant chemotherapy [20]–[22], [26], [28], [32], [33] (HR = 1.32, 95% CI = 1.13–1.55, p = 0.001; I2 = 0.0%, P = 0.71 for heterogeneity) and patients treated by palliative chemotherapy [17], [19], [23]–[25], [27], [29]–[31], [34], [35] (HR = 1.51, 95% CI = 1.26–1.80, p<0.001; I2 = 36.2%, P = 0.11 for heterogeneity, Table 2)
Event free survival
A total of 14 studies composed of 1640 patients reported the event free survival (EFS) in this meta-analysis [16]–[20], [22], [23], [27]–[33], [35]. Among them, one study used the RFS as its endpoint [20], three studies examined the DFS [28], [32], [33], and the rest ten studies evaluated the PFS [16]–[19], [22], [23], [27], [29]–[31], [35]. There was strong evidence to support that the expression of TUBB3 was correlated with the EFS (positive/high vs. negative/low: HR = 1.47, 95% CI = 1.24–1.74, p<0.001; I2 = 37.0%, P = 0.08 for heterogeneity, Table 2, Figure 4).
The stratified analysis by ethnicity showed that the association between TUBB3 and EFS was significant in both Asian [22], [23], [31]–[33], [35] and Caucasian populations [16], [17], [20], [27]–[30] (Asian: HR = 1.65, 95% CI = 1.35–2.02, p<0.001; I2 = 3.3%, P = 0.40 for heterogeneity; Caucasian: HR = 1.27, 95% CI = 1.10–1.46, p = 0.001; I2 = 36.3%, P = 0.14 for heterogeneity, Table 2). Among the 14 studies that reported data on EFS, eight studies used the taxane-based regimen [16], [18], [19], [22], [23], [30], [31], [35], four studies examined the vinorebine-based regimen [17], [20], [32], [33], and three studies investigated both regimens [27]–[29]. The stratified analysis by chemotherapy regimen suggested that the positive or high expression of TUBB3 was correlated with a worse EFS in patients receiving the taxane-based or vinorebine-based regimens, but not in patients treated by the taxane and vinorebine combined regimen (taxane regimen: HR = 2.05, 95% CI = 1.55–2.71, p<0.001; I2 = 0.0%, P = 0.50 for heterogeneity; vinorebine regimen: HR = 1.50, 95% CI = 1.22–1.86, p<0.001; I2 = 0.0%, P = 0.67 for heterogeneity; taxane and vinorebine combined regimen: HR = 1.16, 95% CI = 0.99–1.36, p = 0.075; I2 = 0.0%, P = 0.67 for heterogeneity, Table 2). In the stratified analysis by TUBB3 detection method, three studies used PCR to detect TUBB3 expression [16], [30], [32] and the remaining 11 studies chose IHC to assess TUBB3 expression [17]–[20], [22], [23], [27]–[29], [31], [33], [35]. Our analysis showed that the expression of TUBB3 was significantly associated with the EFS in both groups (PCR: HR = 1.30, 95% CI = 1.14–1.39, p<0.001; I2 = 34.1%, P = 0.13 for heterogeneity; IHC: HR = 1.68, 95% CI = 1.32–2.14, p<0.001; I2 = 11.9%, P = 0.32 for heterogeneity, Table 2). In the subgroup analysis by treatment strategy, four studies evaluated the surgery plus adjuvant chemotherapy [20], [28], [32], [33] and ten studies reported results from the palliative chemotherapy [16]–[18], [22], [23], [27], [29]–[31], [35]. Our analysis showed that the patients with negative or low level of TUBB3 had a longer EFS than the patients with positive or high level of TUBB3 (surgery plus adjuvant chemotherapy: HR = 1.32, 95% CI = 1.12–1.54, p = 0.001; I2 = 0.0%, P = 0.42 for heterogeneity; palliative chemotherapy: HR = 1.63, 95% CI = 1.24–2.14, p<0.001; I2 = 47.1%, P = 0.05 for heterogeneity, Table 2).
Publication bias
Publication bias was evaluated by the funnel plots qualitatively and tested by the Begg's and the Egger's tests quantitatively. Visual inspection of the Begg's funnel plots did not show significant evidences of asymmetry in the ORR, OS, and EFS (figure not shown), suggesting no publication bias in this meta-analysis. In addition, no significant bias was found in the Begg's test and the Egger's test. For the Begg's test, P was 0.17, 0.48, and 0.16 for the ORR, OS, and EFS respectively; for the Egger's test, P was 0.20, 0.07, and 0.06 for the ORR, OS, and EFS respectively (figure not shown).
In this meta-analysis, we explored the predictive role of TUBB3 in patients receiving the taxane/vinorebine-based chemotherapy. We found that the high level of TUBB3 expression was associated with a lower objective response rate (ORR), a shorter overall survival (OS), and a worse event-free survival (EFS) compared to the low level of TUBB3 expression. Consistently, a previous meta-analysis by Zhang et al. [54] reported that TUBB3 was a biomarker for the sensitivity of paclitaxel/vinorebine-based chemotherapy in patients with NSCLC.
We think it is necessary to conduct an updated meta-analysis to re-evaluate the association between the expression of TUBB3 and the efficacy of taxane/vinorebine-based chemotherapy for the following reasons. First of all, the latest studies included in the previous meta-analysis by Zhang et al. [54] were published before 2009. There have been a number of studies with large patient sample size being published since 2009. In fact, our study has a much larger sample size (2401 patients from 28 studies) compared to the study by Zhang et al. (552 patients from 10 studies), which gives more reliable results in our analysis. In addition, Zhang and colleagues only examined the objective response rate and the median survival time in their analysis. In our study, we used the objective response rate, overall survival, and event free survival as the primary parameters to assess the association between the expression of TUBB3 and the clinical outcomes of taxane/vinorebine-based chemotherapy. Because a low ORR suggests tumor resistance to the chemotherapy regimen and a short OS/EFS indicates a poor prognosis, it is necessary to include all three parameters in order to make a comprehensive assessment about the treatment response to a chemotherapy regimen [55]. In our analysis, we demonstrated that the high level of TUBB3 expression was associated with a lower ORR, a shorter OS, and a worse EFS, which strongly supported that TUBB3 had a prognostic value in predicting the treatment response to the taxane/vinorebine-based chemotherapy. Furthermore, we performed a subgroup analysis by the TUBB3 detection method and treatment strategy, which were not done in the study by Zhang and colleagues.
Microtubule is composed of polymers of tubulin dimers and plays an important role in the development and maintenance of cell polarity, vesicle and organelle transportation, cellular signaling, and cell division. Tubulin and microtubules are the main targets of the vinca alkaloids. Vinorelbine binds to the β-subunit of tubulin dimers at a distinct region called the vinca-binding domain. In contrast, paclitaxel binds to β-tubulin within the lumen of microtubule. This binding event affects a protein loop, called the M-loop, which is thought to stabilize the lateral interactions between the adjacent protofilaments of microtubule [12], [57]. Binding of taxane/vinorebine inhibits the association/dissociation of tubulin dimers in microtubule and thus disrupts the spindle dynamics, resulting in cell cycle arrest in the transition from metaphase to anaphase and eventually causes apoptotic cell death [56]. However, the molecular mechanism underlying the association between the expression level of TUBB3 and the sensitivity of taxane/vinorebine chemotherapy remains an unanswered question. Further studies are needed to address this question.
Our meta-analysis showed that the overexpression of TUBB3 may be an important factor for the development of chemoresistance to taxane/vinorebine. Hence, the expression level of TUBB3 may serve as a useful biomarker in the individually-tailored personalized chemotherapy in the future. The patient with low level of TUBB3 may benefit from the taxane/vinorebine-based regimens, whereas those with high level of TUBB3 should avoid the taxane or vinorebine-based chemotherapy and replace them with chemotherapy drugs that can overcome chemoresistance, such as ixabepilone [57].
There are some limitations in our meta-analysis. Firstly, the studies included in this meta-analysis had different study designs, such as the patient selection criteria and chemotherapy protocols. Some studies included radiotherapy in addition to the chemotherapy while the others did not. These differences could contribute to the heterogeneity among those studies.
Secondly, some factors such as age, sex, smoking history, histology type, tumor stage, and treatment method may affect the prognosis in patients receiving chemotherapy treatment. However, we could not conduct a stratified analysis to assess the effects of confounding factors on the predictive role of TUBB3 in NSCLC patients because of the limited information provided in the original publications.
Moreover, the HRs and their 95% CI we extracted from the time-to-event data were not consistent. We have to estimate the HRs by reading the Kaplan-Meier curves because some studies did not report the HRs. Some studies reported the unadjusted HRs while the others provided the adjusted HRs. Moreover, the cofounders they adjusted were not the same for the adjusted HRs. All of these factors more or less contributed to the heterogeneity in this study.
At last, potential publication biases may exist. Articles were not written in English or Chinese and studies failed to get published because of negative or null results cannot be identified in our literature search and thus were not included in this analysis. In addition, some reports did not provide sufficient data were also excluded from our analysis.
In conclusion, our meta-analysis indicated that the expression of TUBB3 may be a useful biomarker to predict the clinical outcomes of taxane/vinorebine-based chemotherapy in patients with NSCLC. With the limitations, heterogeneities, and bias of meta-analysis, our conclusions in this study need to be interpreted with caution. Future large prospective studies with rigorously designed methodology are warranted to confirm our results.
Supporting Information
Checklist S1.
PRISMA checklist.
Table S1.
Quality assessment of eligible studies by the Newcastle-Ottawa Scale.
Author Contributions
Conceived and designed the experiments: LX YLY. Performed the experiments: YLY XPL. Analyzed the data: YLY XPL. Contributed reagents/materials/analysis tools: YLY XPL. Wrote the paper: YLY XPL LX.
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- 38. Wan YY, Hui HX, Wang XW, Sun SA, Wu J (2011) [The correlation between chemotherapeutic efficacy and breast cancer susceptibility gene 1 and class IIIbeta-tubulin protein expression in non-small cell lung cancer patients]. Zhonghua Nei Ke Za Zhi 50: 469–473.
- 39. Guo HQ, Zhao Y (2011) Relationship betwwen the expression level of βIII-tubulin and p53 and chemosensistivity of paclitaxel in advanced and local advanced NSCLC. Oncology Progress 9: 420–423.
- 40. Zhou ZS, Liao XF, Zhen QH, He HJ (2012) Expresion of Survivin、BRCA1 and class IIIβ-tubulin in non-small cell lung cancer and its relationship with resistance to paclitaxel. Journal of Chinese Oncology 18: 806–810.
- 41. Zhang JP, Hu XL, Li GF, Chen RB (2012) Relationship between expression of β-tubulin-III and drug efficacy of paclitaxel in non-small cell lung cancer. Medical Recapitulate 18: 2637–2638.
- 42. Gao LH, Mao GX (2012) The relationship between β-tubulin III expression in tumor cells and chemotherapy sensitivity of patients with NSCLC receiving paclitaxel Journal of Nantong University(Medical Sciences). 32: 188–190.
- 43. Liu P, Wang HX, Wang HL (2013) Relationship betweenβ-tubulin expression and paclitaxel containing regimen with drug resistance in non small cell lung cancer. Journal of Clinical Medicine in Practice 17: 12–15.
- 44.
Wells GA, Shea B, O'Connell D, Peterson J, Welch V, et al. (2003) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available: http://wwwohrica/programs/clinicalepidemiology/oxfordasp (accessed 2012 May 5).
- 45. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, et al. (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92: 205–216.
- 46. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47: 207–214.
- 47. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8: 16.
- 48. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327: 557–560.
- 49. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719–748.
- 50. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.
- 51. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50: 1088–1101.
- 52. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–634.
- 53. Ikeda N, Nagase S, Ohira T (2009) Individualized adjuvant chemotherapy for surgically resected lung cancer and the roles of biomarkers. Ann Thorac Cardiovasc Surg 15: 144–149.
- 54. Zhang HL, Ruan L, Zheng LM, Whyte D, Tzeng CM, et al. (2012) Association between class III beta-tubulin expression and response to paclitaxel/vinorebine-based chemotherapy for non-small cell lung cancer: a meta-analysis. Lung Cancer 77: 9–15.
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- 57. Dumontet C, Jordan MA, Lee FF (2009) Ixabepilone: targeting betaIII-tubulin expression in taxane-resistant malignancies. Mol Cancer Ther 8: 17–25.


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Posted by Terri Steffes / 08 December 2010 /
Bunco Girls Rock!
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Life is full of wonderful things. It is our goal to share with you good food, fun books, and lovely gardens, things we believe nurture your soul....


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233 S Wacker Dr # 2000
Chicago, IL 60606
Allstate Insurance: Timothy Miller
3445 W 111th St Chicago, IL
Farmers Insurance - Andrew Flanagan
6146 N Milwaukee Ave Chicago, IL
We've been using Thilman & Filippini primarily for our bonds. Their knowledge & expertise has proved to be invaluable. They are great to deal with & I would highly recommend them.5


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Kindergarten Registration is ongoing. Click the 'Read More' button for information.
La Glace School is a Kindergarten to Grade 9 school located about 45 kilometres northwest of Grande Prairie on Highway 59.
To learn about the successes of our students, teachers and programs, click the 'Read More' button.
PWSD invites you to become a leader in your community by running for school board trusteeship in 2017. To access PWSD's Election 2017 website, click the 'Read More' button.


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Charlotte Stallard
More ideas from Charlotte
Chocolate Guinness Cake
How to Build a Terrarium — fun, kid-friendly DIY garden project! Not to mention, incredibly low-maintenance.:
My nickname is Button.... New art hobby for me - using buttons!!! Something to ponder...
4 3/8 X 4 3/8 X 3/4 Box Photo: This Photo was uploaded by d0npen. Find other 4 3/8 X 4 3/8 X 3/4 Box pictures and photos or upload your own with Photobu...
The making of the Toothless cake figure from the How To Train Your Dragon cake
Baby Toothless Tutorial by Naera the Cake Dutchess. "How To Train Your Dragon" i am going to try to make this out of clay


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Ruby Friedman
|Ruby Friedman
RFO photo by Kent Geib
|Background information
|United States
|Rock, alternative, jazz, country, blues
|Singer, songwriter, producer, composer
|Vocals, guitar, piano, ukulele, whistling
|Years active
|2009 — present
Ruby Friedman is an American singer/songwriter/composer, with roots in New Orleans, New York, and Los Angeles. She is the leader of the Ruby Friedman Orchestra.[1][2]
The Ruby Friedman Orchestra has been in studio in New Orleans, in New York City with Josh Valleau at The Glass Wall, with Peter Malick [3] at OCL Studios [4] in Calgary, and at his studio in Los Angeles. Final recording, production and mixing were done by Alex Elena[5] and Topher Mohr[6] at Beethoven Studios in Culver City. The band released their debut album, Gem on November 11, 2016.[7] The first single from the album I'm Not Your Friend was released in June 2016[8]
The critically acclaimed version of You'll Never Leave Harlan Alive,[9] was featured prominently in the Season Five finale of Justified. Graham Yost, creator and Executive Producer of the series, discussed the use of the Ruby Friedman version in the show.[10]
Her version of the song[11] was also selected for use in the Reveal[12] documentary, The Dead Unknown,[13][14][15] an investigative report on a 1969 cold case regarding the disappearance and murder of a young woman, in Harlan, Kentucky, in June 1969.
In late 2015, The Golden Globe Award and Emmy Award winning Amazon Studios TV show, Transparent selected the arrangement featuring her vocals on the Gina Villalobos/Eric Colvin[16] produced version[17] of the Sly and the Family Stone hit Family Affair for use in the trailer[18] promoting the launch of Season 2.
In 2015, Ruby Friedman performed the haunting vocals on the song, Hunt You Down[19] for the CLIO award winning[20] advertising campaign for the launch of the Sony PS4 game, Bloodborne.[21][22][23][24] The song is a collaboration with The Hit House Music,[25] and was written by Scott Miller and William Hunt. It was recorded by Wyn Davis[26] in Los Angeles, and by Ruby Friedman at Word of Mouth Recording Studios in New Orleans. The Petrol Advertising campaign using the song won the coveted Golden Trailer Award for best Video Game TV Spot.[27] The song was released as a successful single in conjunction with the general availability of the game.[28]
In March 2015, the EP, Song of the Demimonde was released, containing 7 tracks of her most-requested cover material. House of the Rising Sun, the last song on the EP,> was recorded at Word of Mouth Recording Studios in New Orleans with renowned New Orleans piano player Tom McDermott,[29] and longterm Smashing Pumpkins violinist, Ysanne Spevack.[30]
When in New Orleans, she performs with Tom McDermott[31] and Friends, (recurring musician from the HBO [32] Emmy Award and Grammy Award nominated TV series, Treme),[33][34] including Ysanne Spevack,[35] at the renowned Buffa's.[36] In both April 2015 and 2016, she performed at Buffa's and at the Lagnaippe Stage for Jazzfest[37] with Tom McDermott and Friends, including Aurora Nealand.[38] During the 2015 Jazzfest week, she also performed with Tom McDermott at the Just the Keys, Please private house concert, hosted by the esteemed Harry Shearer.
She has been retained by the estate of the legendary 20th Century Academy Award film song composer Harry Warren[39] to re-imagine and record some of the extensive Harry Warren catalog. The catalog consists of hundreds of songs, from the familiar Academy Award winners to unfinished works in process. Several of these recordings, Rose Tattoo, Ungrateful Heart, and Welcome to the Party are included on the Song of the Demimonde EP.
In 2014, Ruby Friedman was commissioned to perform two songs, including the title track, on a tribute album, Life, honoring the life and music of Tarka Cordell,[40] (produced by Alex Elena). Other notable contributing vocalists on the album include Lily Allen, Imani Coppola, and Evan Dando.
Her original song, Shooting Star, was selected for promotional use on the television program America's Got Talent and has been licensed internationally for continued use in that franchise. The song has also been licensed for use by Fox Sports. The original song, Drowned, was featured in Season Three's most memorable scene of the television show, Sons of Anarchy.
Her unique multi-octave vocal stylings have her much in demand, and she has been requested to perform versions of End of the World, Needle in the Hay, Angel Eyes, Pale Blue Eyes, Crazy, and I Want You, She's so Heavy for various compilations.[41]
When in Los Angeles, she has headlined at The House of Blues,[42] The Troubadour,[43] The Viper Room,[44] Hotel Cafe, Los Globos,[45] Echoplex,[46] and Pershing Square. She has made numerous invited guest appearances, including performances with Donovan, with Grammy Award nominee Scott Healy,[47] with the Jeff Goldblum [48] jazz ensemble, and at many events at the Sayers Club.[49] When in New York City, she performs with Grammy Award winning Vince Giordano and the Nighthawks of Boardwalk Empire fame.[50] She performed an acoustic invitation only show, at the Turn Gallery in Soho,[51] accompanied by Imani Coppola,[52] Matthew Steer, Maiya Sykes, Ben Crippin Taylor, and Conor Brendan.[53]
|Release Date
|Drowned (Single)
|Life (Single)
|Room 609 Records
|Home or Out of Range (Single)
|Room 609 Records
|You'll Never Leave Harlan Alive (Single)
|Song of the Demimonde (EP)
|Hunt You Down (Single)
|The Hit House
|I'm Not Your Friend (Single)
|Gem (Album)
|House of the Rising Sun (feat. Tom McDermott & Ysanne Spevack) (Single)
- ^ Ruby Friedman Orchestra official site
- ^ Ruby Friedman Orchestra Published Music
- ^ Peter Malick website
- ^ Dan Owen's OCL Studio website
- ^ Alex Elena official site
- ^ Topher Mohr Official Site
- ^ Digital Journal Article
- ^ Pop Matters Review \
- ^ You'll Never Leave Harlan Alive Video
- ^ Graham Yost EW Justified Season 5 Post-Mortem
- ^ You'll Never Leave Harlan Alive Video
- ^ Reveal CIR Main Site
- ^ Dead Unknown Part 1 Mountain Jane Doe
- ^ The Dead Unknown Part 2 The Exhumation
- ^ The Dead Unknown Part 3 What Secrets Lie Beneath
- ^ Feverpitch Web Site
- ^ Family Affair Stream
- ^ Official Amazon Studio Transparent Season 2 Trailer
- ^ Hunt You down - single
- ^ CLIO Key Art Awards
- ^ Bloodborne Official site
- ^ Bloodborne YouTube PS4 30 Second The Hunt Begins TV Commercial
- ^ HitHouse Soundcloud Bloodborne Hunt You Down 30 second mix
- ^ Bloodborne YouTube PS4 90 second Cut You Down (The Hunt Begins) trailer
- ^ The Hit House official site
- ^ Total Access Recording Page
- ^ Award Winners List
- ^ Hunt You down - single
- ^ Tom McDermott Official Page
- ^ Ysanne Spevack Official Page
- ^ NPR article on Treme
- ^ HBO Treme Official Site
- ^ Tom McDermott Official Page
- ^ St Louis Article
- ^ Ysanne Spevack Official Page
- ^ Buffa Official Page
- ^ New Orleans Jazz and Heritage Festival Official Page
- ^ Aurora Nealand Official Page
- ^ Harry Warren Music website
- ^ Tarka Music official site
- ^ Ruby Friedman Soundcloud site
- ^ House of Blues official site
- ^ The Troubadour Official site
- ^ The Viper Room Official site
- ^ Club Los Globos Official site
- ^ The Echo Official site
- ^ Scott Healy Official Page
- ^ Jeff Goldblum at the Rockwell website
- ^ SBE Sayers Club official site
- ^ Vince Giordano official site
- ^ Turn Gallery Official site
- ^ Imani Coppola official site
- ^ Conor Brendan Reverbnation site
External links[edit]
- Ruby Friedman Orchestra Published Music
- Ruby Friedman Official Site
- America's Got Talent Official Site
- Sons of Anarchy Official Site U.S. only
- Sons of Anarchy Official Site Canada
- Justified Sony Official Site
- Justified FX Official Site U.S. only
- Justified Official Site Canada
- Bloodborne PS4 site
- Amazon Transparent Season 2 site


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5 Bedrooms Detached House for sale
Cornwallis Avenue, Folkestone CT19
Prestigious property just 0.5 mile by foot to folkestone central train station 0.4 mile by foot to harvey grammar. 4 reception rooms, 5 double bedrooms - 3 with en-suites, garage and…
4 Bedrooms Detached House for sale
Broadfield Road, Folkestone, Kent
Spacious and beautifully presented four double detached family house with luxury family bathroom & two en-suite shower rooms. remaining national house building council warranty…
Martin&co are delighted to offer this six bedroom semi-detached home in the sought after location of folkestone's west end. this house has been a family home for nearly forty…
£400,000 Offers in Excess of
Godwyn Road, Folkestone, Kent, England
Occupying the whole first floor of a wonderful period building, this three bedroom apartment is beautifully presented. through the entrance hall is the modern kitchen with breakfast…
4 Bedrooms Maisonette Flat for sale
Turketel Road, Folkestone, Kent
Be the envy of all your friends and loved ones in this exclusive and extremely well located west end apartment.
Grimston Avenue, Folkestone, CT20
A stunning top floor apartment situated in the extremely sought after location of grimston avenue. comprising of an entrance hallway, kitchen, three double bedrooms, fantastic lounge…
£245,000 Guide Price
Sandgate Road, Folkestone, Kent, CT20
An extremely spacious 3 bedroom ground floor flat with private garden requiring some updating and modernisation.
£245,000 Offers Over
Sandgate Road, Folkestone, Kent
An exceptional apartment that has been renovated to an impressive standard and has space to accommodate families or people looking for a second home that need to commute into london.
£245,000 Guide Price
Sandgate Road, Folkestone, CT20
This is a beautiful top floor apartment in the west end of folkestone and close to the train station. the apartment has been fully modernized throughout and now has many additional…
£160,000 Offers Over
3 Bedrooms Duplex Flat for sale
Westbourne Gardens, Folkestone, Kent
This is a great apartment in the much sought after west end area of folkestone; a great buy with a lengthy lease.
2 Bedrooms Apartment Flat for sale
Westbourne Gardens, Folkestone, Kent
Chain free! a great investment for cash buyers only and priced accordingly; this spacious flat comes with a low lease.
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Under £5
2008 Cono Sur Tesco Chilean Reserva Sauvignon Blanc
This new vintage, cool climate sauvignon blanc from Chile's Pacific-influenced Casablanca Valley is refreshing and aromatic, displaying the classic gooseberryish fruit of the grape with a citrus zing. £4.69, Tesco
Under £10
2006 Zefyro, Alentejo
Dense in colour with bright brambly fruit on the nose, this Alentejo red shows typical southern Portuguese richness with plenty of mulberry and damson jam fruitiness and juicy tannins. One for roast pork and crackling. £8.99, Booths
Splash out
2004 Muga Reserva Seleccion Especial
From a great vintage for Rioja, this classy blend of mainly tempranillo, plus garnacha, mazuelo and graciano, is traditional in style, with smoky vanillan aromas and a rich, chocolate-tinged palate of dark cherry. £18.99, WaitroseReuse content


text: So you've started a business. What are the next steps that you should take to insure that your new business stays afloat? In this presentation, we will look at ways to improve your "business life" and begin good habits that will help you keep this new business afloat. We will look at several ways to help you achieve financial success in the early stages of your new business, including different ways to fund your new business and look at good bookkeeping habits to easily track your revenue and expenses and your business grows.


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Love the food here. Large portions. Worth the price. Parking is pretty hard to get if you're late. Also, wait is longer if you're late.
1 - 10 of 83 reviews
Love the food here. Large portions. Worth the price. Parking is pretty hard to get if you're late. Also, wait is longer if you're late.
I was just looking for a place with good pancakes which just happen to be around the Ala Moana area and so, as I always do, relied on Yelp to recommend me some places. Yogur story seemed like the closest as I work within the...More
Don't judge it from the outside or location. Inside decor is modern. The purple pancakes and syrup are surprisingly light and not overly sweet. The other breakfast items were unique twists on favorites. Something for everyone. My local friend told me that during busy times...More
My daughter took me here to experience the Ube Pancakes and they were amazing! The atmosphere was relaxed and fun. The service was excellent!
Super nice pancake and services! What we ordered was • Guava juice •Taro pancake As this taro pancake has been famous in Japan, we couldn't help but having it. The taste was a bit different from what I imagined, which tasted more sweet potato, which...More
From the outside it looks like it's a small hole in the wall restaurant. Boy was I wrong! When you enter, the room is very spacious and also has an upstairs area. They have a bar as well. The design of the place is very...More
I have watched this place on IG and drool on every single picture they post. Finally made it and was not disappointed. We ordered the Ube Pancakes (that purple ube coconut syrup is to DIE for), fresh fruit waffle and crab cake benedict. All on...More
Probably my best meal in Honolulu! I found out about this place while doing research on food spots to visit with my epicurean friends. It was the ube pancakes that drew me, and so our group of 7 went on a Friday morning, right when...More
Recommended to us by our local friends, this place lived up to the hype! Our server was super welcoming, calling us "Family" throughout the meal and showing us true Aloha spirit. It's tucked in a small strip mall, but inside has tall ceilings, beautiful tree...More
Sunday morning, came expecting a crowd, sat down right away, hostess said crowd comes after 9:00am, very good coffee served to us immediately, ube pancakes were strange looking and the most delicious I've ever eaten . Smoked salmon benedict was also delicious, poached eggs cooked...More


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Chilled Out Desserts Recipes
Pumpkin Pie French Toast…perfect for an Autumn breakfast
Pizza Sliders made with Grands biscuits- Someone needs to make me some of these, haha!
Caramel Pretzel Chocolate Chip Cookies
Super simple Halloween sheet cake…
Crepes, Dulce de Leche, Honey Whipped Cream and Strawberry Sauce
Brown Sugar Baked Peaches
Barbecue Beer Chicken
If you're in charge of bringing the rolls…these are the ones that will "wow" the…
smashed watermelon, vodka, lime juice, and ginger ale.
OMG!! This is AMAZING! Creamy Lemon Pie! Butter, eggs, milk, lemon juice and and vanilla,…
chocolate desserts – Google Search
German Chocolate Pecan Pie Bars
Not sure what to do with all those vegetables? Try these 30 Garden Fresh Side…
Quick Chicken Tortilla Bake. Probably one of my favvvv dishes!
Pumpkin No Bake Energy Bites
Feta and Sun-Dried Tomato Dip. Ingredients: 4 ounces crumbled Feta, 1 cup low-fat Greek yogurt,…
Toffee Crunch Cupcakes Makes 12 cupcakes | Preparation: Position a rack in the lower third…
Strawberry Cheesecake Salad – The BEST salad to bring to any potluck!
make ruffle flowers
Pumpkin Better Than… Cake
Blueberry Sweet Rolls with Lemon Glaze.
Famous perogie recipe that I frequently use. Soo easy and sooo good.
Chicken parmesan grilled cheese
Chili Rellano Breakfast Casserole- BEST breakfast dish ever.
omg!! i found it
Pecan Lace Praline Cookies – Other Pinner: My Very Favorites!!!… Almost like having a Pecan…
Pizza Hut Retro Taco Pizza -This was my favorite!
90 Healthy No-Heat Lunches for Taking to Work
24 Awesome Muffin Tin Recipes
Yummy Grilled Zucchini I am so trying this Pioneer Woman recipe.
Easiest Baked Ziti
Spinach Artichoke Bites
Pigskin Smashed Potato Poppers
Stuffed Pizza Muffins � Easy Healthy Recipes � aci
20 Salsas, Sauces, and Toppings for Grilled Food
Cinnamon roll waffles – Cody would LOVE these!
Peach Pie- crust melts in your mouth
Chimichurri Champion
lavender hot chocolate. I love all things lavender!


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Evening entertainment: Camping & Holiday Parks in ShardlowView results on a map
3 bookable sites within 40 miles of Shardlow
Coalville, Leicestershire, England Show on map
|Non-electric hardstanding touring pitch
|4 x
|From £10/€11.38/A$16.82/US$12.68/CA$16.78/CHF12.33/kr111.36/kr84.96/kr107.76/kr1,316/$206.61/$8,333/PEN41.46/NZ$17.49/R164.74/zł48.29/R$42.43/Kč299.40/RSD1,389 per night
|Electric hardstanding touring pitch
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Ashbourne, Derbyshire, England Show on mapLast booked
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Kendra comes back from working out and finds footboy laying on the floor next to the couch. If you saw her previous pantyhose video "Claire sends foot boy to executive friend Kendra" you would have seen her telling him to stay there until she got back from her workout. Any way he explains the couch smelled like feet. Kendra is upset but, is okay with him being on the floor as she plans to assault his face with her not so fresh wet ripe socks after her run. These things are really wet and damp and the room is filled with her smelly scent. He doesnt even notice that she is swinging his chastity keys around her finger. He notices "you have my keys" You don't think Claire would send him to Kendras without him being locked up in chastity. Actually Claire did not lock him completely up. Instead of attaching the cage portion to the cock ring behind his balls, she puts on one of the smaller size rings that come with the chastity kit. By placing the ring in place of the cage, it actually traps his balls between the ring squashing them quite tight and any stimulation gives him swollen blue balls. Kendra wants to see the predicament he is in and has him remove his pants. Kendra loves it but tells him he is not getting unlocked. She sits downs and removes her tennis shoes and places her ripe damp wet socks on his face. These socks are way more overpowering than the pantyhose if that is even possible. THEY STINK!!! Claire had mentioned to Kendra feel free to torture his cock and balls and that is just what she does. While she smothers him with her socks and then her bare feet she makes him stroke his cock to the brink, then commands stop stroking once his cock an balls are swelling. She slaps his balls with the riding crop while continuing to smother his face. Once again she tells him to start stroking slow, and he does, but eventually he starts to rapidly stroke his cock, as he has not been allowed to cum in some time. I guess he thinks he could get a orgasm as his cage is not completely locked up. This is pissing Kendra off, so she beats his balls harder, but he keeps on stroking. Harder and harder she beats his balls until he can't take anymore and takes his hands away. Kendra is pissed and grabs his cock between her feet and beat his purple helmet with the riding crop until she is satisfied that he is sorry for stroking uncontrollably.
She has told me that I will now be doing not only my household chores, I will also be doing hers. One of her chores is to keep the kitchen and floors clean. She comes home and finds the kitchen and floors a complete mess. She makes me strip nude, and reminds me of the footage she recorded on her laptop which actually turned out to be her moms panties! I Fucked up big time! She then destroys my ass with a thin leather strap. Ouch!!!!
Kendra knows you like smelly wet socks and sweaty feet after she has been working out. She gets your pants off and gets you kneeling right up close to her moist socks and feet.She thinks you are such a loser for liking smelly feet, but she is willing to control your stroking rate while she teases you with her damp ripe socks. Her socks come off and she gets you spitting in your hand and jerking it faster and faster until her oh so cruel countdown.
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Original Run - 2011 To Present Main Cast - Eliza Coupe, Elisha C
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Old First Ward
COST:General Admission: $15
Student Admission: $5
Explorer Pass Holders: FREE
Upcoming Dates:
Sunday, July 2 – 1 PM
Saturday, July 8 – 4 PM
Friday, July 14 – 6 PM
Sunday, July 16 – 1 PM
Saturday, July 22 – 4 PM
Friday, July 28 – 6 PM – TOUR MOB
$5 Admission, No Advance Reservations
Friday, August 4 – 6 PM
Sunday, August 6 – 1 PM
Saturday, August 12 – 4 PM
Tuesday, August 15 – 6 PM
Friday, August 18 – 6 PM
Sunday, August 20 – 1 PM
Saturday, August 26 – 4 PM
Tuesday, August 29 – 6 PM
Join us for a walking tour of one of the oldest neighborhoods in Buffalo! The First Ward is the neighborhood adjacent to the Buffalo River, located in the shadows of the grain elevators that employed many of the neighborhood's residents. On this tour, you will learn about how the growth and development of the neighborhood was closely tied to the rise of the grain trade at Buffalo's harbor. A neighborhood with a proudly Irish heritage, the First Ward has been the birthplace and home to some of Buffalo's most famous citizens, including Michael Shea, Jimmy Slattery, and Fingy Connors. Come on this tour to learn their stories and many more! The tour will end at Gene McCarthy's Tavern and Old First Ward Brewing, the perfect place to enjoy a pint after the tour.
Meet at Mutual Riverfront Park at 41 Hamburg Street, Buffalo, NY 14204. Street parking is available on Hamburg and South Streets by the park – please do not use the parking lot for the Waterfront Memories & More Museum.
- Advance reservations are encouraged but not required for this tour.
- All credit card payments must be made in advance. Advance reservations with a credit card can be made online until the tour starting time. Cash or checks are accepted at the start of the tour.
- If you make an advance reservation, please print your confirmation email, or be prepared to show it on your phone.
- This tour is approximately two hours in length.
- Please wear comfortable walking shoes and dress for the weather – the tour will proceed rain or shine.
- Cameras are encouraged!